Using a combination of three mutations, SARS-CoV-2 variants can be created

The researchers tested how three mutations altered the interaction between a key part of the virus (gray) and the human protein to which it attaches (orange). Credit: Biochemistry 2022

The SARS-CoV-2 virus has been buffeting the planet like a ship battered by storm seas. Observant scientists have now detected a pattern: many of these variants share the same trio of mutations. ACS Biochemistry published a study looking at the impact of these mutations on the function of a crucial viral component. This triad modifies the features it needs to trigger and sustain COVID-19 infection, according to their research.

As a result of the SARS-CoV-2 virus causing human cells to repeatedly reproduce its genetic code, mistakes have been discovered. These mistakes, or mutations, serve as the starting point for the development of new varieties. Three mutations at locations K417, E484 and N501 have been discovered in approximately half of the genomic sequences within variations.

SARS-CoV-2 may infect human cells by latching onto their ACE2 protein thanks to all of these modifications to the virus’s receptor binding domain. This mix of mutations provides the virus with advantages that can’t be achieved with a single modification alone. Each of these three mutations has to be examined individually and in combination in order to determine the benefits and downsides.

To begin, scientists created domains incorporating mutations and tested the effects on cells cultured in Petri plates as an initial step. The researchers examined the domain’s stability, capacity to bind to ACE2, and resistance to antibodies, in addition to how well cells could manufacture it. At least one of these qualities is enhanced by each mutation, albeit at a price.

A modification in K417, for example, enhanced the synthesis and stability of the domain, as well as its capacity to evade a particular antibody. However, the domain’s capacity to connect to ACE2 was also reduced. The strengths and drawbacks of the other two mutations were somewhat different. However, when all the adjustments were combined, the detrimental impacts of each one were lessened. However, the domains with all three mutations were capable of binding extremely firmly to ACE2 and evading two types of antibodies, yet they were also produced at the same level and were the same stable. New insights on virus evolution can be gained from these findings, say the researchers.

Further information: Vaibhav Upadhyay et al, Convergent Evolution of Multiple Mutations Improves the Viral Fitness of SARS-CoV-2 Variants by Balancing Positive and Negative Selection, Biochemistry (2022). DOI: 10.1021/acs.biochem.2c00132

Journal information: Biochemistry

Source: American Chemical Society